A DNA vaccine encoding CCL4/MIP-1β enhances myocarditis in experimental Trypanosoma cruzi infection in rats

Ester Roffê, Adriano L.S. Souza, Bráulia C. Caetano, Patrícia P. Machado, Lucíola S. Barcelos, Remo C. Russo, Helton C. Santiago, Danielle G. Souza, Vanessa Pinho, Herbert B. Tanowitz, Elisabeth R.S. Camargos, Oscar Bruña-Romero, Mauro M. Teixeira

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Chagas' disease, caused by Trypanosoma cruzi, is a major cause of cardiovascular disease in Latin America. Exacerbated inflammation disproportional to parasite load characterizes chronic myocardial lesions in chagasic patients. Chemokines and their receptors are expected to account for the renewed inflammatory processes after the inoculation of the parasite, but their potential unique functions are far from being clear. Herein, we evaluated the effect of a DNA vaccine encoding CCL4/MIP-1β, a CC-chemokine, in T. cruzi-elicited myocarditis in rats. Holtzman rats were given intramuscularly cardiotoxin and the CCL4/MIP-1β DNA-containing plasmid (100 μg) was delivered in this muscular site four times. Fourteen days after last immunization, animals were inoculated with a myotropical CL-Brener T. cruzi clone. Peak of parasitism was observed at day 15 after infection, preceding the peak of myocardial inflammation at day 20. Myocarditis was still intense at day 30, but the inflammatory infiltrates showed a more focal distribution. The expression of CCL2/MCP-1 and CCL4/MIP-1β correlated closely with the kinetics of myocardial inflammation. The CCL4/MIP-1β DNA vaccine induced an increase of the levels of the anti-CCL4/MIP-1β observed in T. cruzi-infected animals. This was associated with an exacerbation of myocardial inflammation and fibrosis, although alterations in parasitemia and myocardial parasitism were not observed. Our data suggest that CCL4/MIP-1β plays a role in preventing excessive inflammation and pathology rather than in controlling parasite replication.

Original languageEnglish (US)
Pages (from-to)2745-2755
Number of pages11
JournalMicrobes and Infection
Volume8
Issue number12-13
DOIs
StatePublished - Oct 2006

Keywords

  • CCL4/MIP-1β
  • Chemokine
  • DNA vaccine
  • Myocarditis
  • Trypanosoma cruzi

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

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